The synthesis and biological evaluation of the narcotic antagonists which are the subject of this proposal may assist in answering the following: 1) Is the association between psychotomimetic effects and analgesia in the narcotic antagonists fortuitous? 2) Is the drug-seeking behavior associated with the withdrawal syndrome related to a high agonist-antagonist ratio? 3) Can the duration of action of narcotic antagonists be prolonged by appropriate substitution on the nitrogen and/or nucleus? Our work has now indicated that the answer to the last question is affirmative. We plan to continue our studies in the effect of varying the substituents on the nitrogen atom of the hexahydro-2,6-methano-benzazocine nucleus in order to increase potency while maintaining a long duration of action. We also plan to replace the 14 beta-hydroxyl group in the morphinan ring system in order to improve potency and duration of action. In view of the current shortage of codeine, a total synthesis of this alkaloid is proposed which invalues relatively simple intermediates and reagents.